JOURNAL OF POLYMER SCIENCE
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2025
·
IF 3.6
Sunqi Yu,Siyuan Chen,Tianrui Tong,Yunfeng Yan,Qi Shuai
Micelle-based drug delivery systems (DDS) have emerged as a promising solution to address challenges associated with the in vivo delivery of hydrophobic anticancer chemotherapeutics. However, micelles still encounter issues such as drug pre-leakage and poor stability in physiological conditions. To overcome these limitations, we developed a core-cross-linking strategy utilizing amphiphilic copolymers, mPEG- b- P(AVL- co -LA) (mPPAL), functionalized with phenylboronic acid (PBA), and catechol by CuAAc “click” chemistry, respectively. These copolymers self-assembled into core-cross-linked micelles (CLMs), featuring boronic ester bonds, which were characterized through a series of evaluations. The CLMs exhibited a rational particle size, uniform morphology, low critical micelle concentration (CMC), high PTX loading capacity, and excellent stability. Two promising micelles, CLM1 and CLM3, were identified, and their responsiveness to acidic pH and elevated levels of ROS was confirmed to enable controlled PTX release. The results of MTT assay and hemolytic analysis demonstrated high biocompatibility and potential in vivo application of these selected CLMs. The anticancer efficacy of the selected PTX-CLMs was further validated through MTT assay and 3D tumor spheroid studies. Fluorescence microscopy and flow cytometry demonstrated rapid intracellular uptake of the CLMs. In vivo biodistribution studies demonstrated successful accumulation in the targeted tumor tissue. These findings suggest that the boronic ester-based CLMs developed in this study are a promising nanocarrier for effective PTX delivery. Graphical Phenylboronic acid (PBA) and catechol-modified amphiphilic copolymers (mPPAL@R) were synthesized via ring-opening polymerization followed by CuAAc click chemistry. These copolymers were employed to construct pH- and ROS-dual-responsive micelles with boronic ester core-crosslinking. A series of in vitro and in vivo experiments were conducted to evaluate PTX-loaded micelles, demonstrating their significant potential for effective PTX delivery.
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International Journal of Nanomedicine
·
2024
·
IF 6.6
Pilong Shi,Yuetong Sha,Xinran Wang,Tao Yang,Jiawei Wu,Jiajun Zhou,Kai Liu,Xue Guan,Song Wang,Yongsheng Liu,Jingquan Gao,Hongli Sun,Tao Ban,Yonggang Cao
Purpose Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Cunliang Guo,Lilong Du,Xiaoxun Du,Rui Gao,Xinyi Jiao,Zhenhua Li,Tongxing Zhang,Pingsheng Huang,Chuangnian Zhang,Zujian Feng,Weiwei Wang,Baoshan Xu
Intervertebral disc degeneration (IVDD) is closely associated with mitochondrial dysfunction caused by the excessive accumulation of reactive oxygen species (ROS). Current therapeutic strategies are limited in their ability to precisely intervene in mitochondrial dynamics imbalance. This study develops a ROS-responsive hydrogel crosslinked via dynamic borate ester bonds between boric acid-modified hyaluronic acid and polyvinyl alcohol (PVA), which was further loaded with berberine liposomes (HP-Lipo@BBR), aiming to scavenge excessive ROS, and restore mitochondrial function. The hydrogel exhibited excellent degradability, injectability, self-healing properties, antioxidative effects, and biocompatibility. It triggers intelligent drug release in the high-ROS microenvironment of degenerated discs. The liposomes efficiently encapsulate berberine, facilitating intracellular drug delivery via the endocytosis of nucleus pulposus cells. Mechanistically, berberine scavenges ROS, inhibits abnormal phosphorylation of dynamin-related protein 1 (p-Drp1), and reduces excessive mitochondrial fission, thereby blocking the caspase-3-mediated apoptosis pathway. In a rat disc puncture degeneration model, intradiscal injection of HP-Lipo@BBR effectively maintains intervertebral disc height and the hydration of nucleus pulposus tissue, inhibits mitochondrial fission-apoptosis axis, and improves the regeneration of extracellular matrix, with therapeutic effects significantly superior over free berberine or hydrogel. This study provides a new strategy for minimally invasive treatment of IVDD and other related degenerative diseases.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Haihui Xing,Xuan Sun,Lei Xing,Qiaoyun Li,Mingjie Puyang,Lihua Liu,Dan Chen
Alzheimer's disease (AD), a prototypical neurodegenerative disorder, is pathologically characterized by amyloid-β (Aβ) deposition, hyperphosphorylated Tau protein accumulation, and oxidative stress cascades. Current therapeutic strategies are constrained by limited blood-brain barrier (BBB) penetration efficiency and insufficient targeting specificity. This study developed a brain-targeting intelligent nanodelivery system (CC-Ang@ECR) based on the natural pleiotropic neuroprotectant ecdysterone (ECR) to synergistically modulate AD pathological networks. The system employs carboxymethyl chitosan (CMCS) as the backbone, functionalized with hydrophobic 4-carboxyphenylboronic acid (CPBA) to construct a ROS-responsive amphiphilic polymer (CMCS-CPBA, abbreviated as CC), and further modified with Ang-2 peptide for targeted engagement of LRP receptors on BBB endothelial cells, enabling efficient brain delivery. The nanocarrier encapsulates hydrophobic ECR via hydrophobic interactions, achieves BBB transcytosis through Ang-2 peptide mediation, and releases ECR precisely in AD lesions via CPBA hydrolysis triggered by elevated ROS microenvironments. In vitro and in vivo studies demonstrate that CC-Ang@ECR effectively scavenges excessive ROS, suppresses oxidative stress, attenuates aberrant Aβ deposition, downregulates pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), inhibits neuronal apoptosis, and ultimately ameliorates cognitive and motor impairments. This system overcomes the BBB limitations and off-target risks inherent to conventional therapies, providing an innovative solution for synergistic AD therapy.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jiayang Luo,Luyao Xu,Jing Feng,Kexin Xu,Peilin Tian,Xianyue Bai,Shihao Xu,Liewei Wen,Cuixia Lu,Jiaxing Song
Photodynamic therapy (PDT) induces apoptosis in cancer cells by generating cytotoxic reactive oxygen species (ROS); however, this effect is constrained by the intrinsic antioxidant mechanisms of the cells and the hypoxic conditions of the tumor microenvironment (TME). To overcome these limitations, a novel ferroptosis-boosted nanophotosensitizer (FCE NPs) is developed after loading alkaloid evodiamine based on an acid-responsive nanoplatform (FC NPs) composed of ferric ions and Chlorin e6 (Ce6). Upon exposure to laser irradiation, the photosensitizer Ce6 efficiently generates singlet oxygen (1O2), which depletes glutathione (GSH), thereby disrupting the redox homeostasis within tumor cells and leading to the oxidation of cellular unsaturated lipid into lipid peroxides (LPO). Additionally, the Fenton reaction between released Fe(III) ions and H2O2 in the TME produces highly cytotoxic hydroxyl radicals (•OH), a form of ROS, causing the accumulation of LPO together with 1O2 to trigger ferroptosis. Following the incorporation of evodiamine, the integrated nanoplatform FCE NPs exhibited excellent antitumor activity through high-performance ferroptosis by inhibiting a glutathione peroxidase 4 (GPX4) level. It was also observed that the key regulator of Wnt signaling pathway β-catenin was downregulated, suggesting the inhibition of FCE NPs on the Wnt signaling pathway. Therefore, this study demonstrated that the FCE NPs could lead to the explosive production of ROS and simultaneous inhibition of GPX4/GSH pathways and the Wnt signaling pathway in colorectal cancer, significantly amplifying the tumoricidal efficacy of PDT through the synergistical sensitization of ferroptosis. This approach offers a promising strategy for the clinical application of ferroptosis therapy.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Teng Liu,Mingyan Yang,Yawen Yu,Xinxin Bai,Yaping He,Fei Yao,Yami Wu,Guangcan Zhou,Yanmei Wang,Dong Qi,Huaying Fan
Acute kidney injury (AKI) is a common clinical syndrome characterized by a rapid decline in kidney function, with inflammation being a key driver. In this study, the hydrophobic drug Rhein was conjugated to hyaluronic acid (HA) via esterification of its carboxyl group. The HA was then modified with 4-hydroxymethylphenylboronic acid pinacol ester (PBAP), which is responsive to reactive oxygen species (ROS). Finally, curcumin was loaded onto this construct to develop a ROS-responsive nanodelivery system (RHP@Cur). In vitro, the nanoparticles showed good ROS responsiveness in H 2 O 2 medium and successfully targeted the CD44 receptors on macrophages. Compared to curcumin alone, RHP@Cur significantly inhibited the secretion of NO and TNF-α and blocked NF-κB activation, with more pronounced effects. RHP itself also exhibited some anti-inflammatory effects. In an in vivo AKI model, the anti-inflammatory effects of RHP@Cur were consistent with the in vitro results. H&E staining results showed that RHP@Cur significantly improved kidney pathological damage. Immunohistochemical results revealed that it reduced the deposition of kidney injury molecule-1 (KIM-1) in the kidneys, with better effects than curcumin and RHP. These results suggest that Rhein exerts a synergistic anti-inflammatory effect, and its potential for combined use with curcumin for kidney therapy makes RHP@Cur more effective than RHP in treating AKI. In addition, since RHP@Cur delivers Cur, it enhances the therapeutic effect of Cur. Therefore, RHP@Cur provides a potential effective means for the treatment of acute kidney injury.
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ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 50
·2106106
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IF 18.808
Jie Shen,Huizhu Yu,Yimeng Shu,Ming Ma,Hangrong Chen
The efficacy of cancer therapy with reactive oxygen species (ROS) as the main therapeutic medium suffers from a deficiency of oxy-substrates, for example, insufficient endogenous hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT) and inherent hypoxia in photodynamic therapy (PDT). Herein, a smart polyethylene glycol (PEG)-ylated nanosystem CaO 2 @ZIF-Fe/Ce6@PEG (abbreviation as CaZFCP) is constructed to achieve H 2 O 2 /O 2 self-supply and Ca 2+ overloading in tumor cells simultaneously for enhanced CDT/PDT. Under the weakly acidic tumor microenvironment, the activity components inside CaZFCP, that is, CaO 2 nanoparticles, Fe 2+ , and photosensitizer Chlorin e6 (Ce6) are released by the degradation of zeolitic imidazole framework-90 (ZIF-90). Thereinto, CaO 2 nanoparticles are further decomposed to generate H 2 O 2 and O 2 , which alleviates both the insufficient endogenous H 2 O 2 and hypoxia in tumor area, thus enhancing the efficiency of CDT and PDT by producing more hydroxyl radicals and singlet oxygen. Furthermore, Ca 2+ overloading induced by the decomposition of CaO 2 is available for amplifying intracellular oxidative stress, resulting in mitochondrial dysfunction, which further improves the efficacy of combined CDT/PDT. In vitro and in vivo experimental results confirm excellent tumor inhibition effect, which also provides a facile paradigm in ROS-involved cancer therapies.
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Bioactive Materials
·
2024
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IF 18
Jian Li,Jvhong Zhang,Pengcheng Yu,Han Xu,Meihui Wang,Zhebin Chen,Bo Yu,Jing Gao,Qiao Jin,Fan Jia,Jian Ji,Guosheng Fu
Vascular diseases seriously threaten human life and health. Exogenous delivery of nitric oxide (NO) represents an effective approach for maintaining vascular homeostasis during pathological events. However, the overproduction of reactive oxygen species (ROS) at vascular injury sites would react with NO to produce damaging peroxynitrite (ONOO − ) species and limit the therapeutic effect of NO. Hence, we design a ROS-responsive NO nanomedicine (t-PBA&NO NP) with ROS scavenging ability to solve the dilemma of NO-based therapy. t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate (ECA) to the injury sites via collagen IV homing peptide. The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging, endoplasmic reticulum and mitochondrial regulation. It subsequently maximizes vascular modulation effects of NO, without production of harmful compounds, reactive nitrogen species (RNS). Therefore, it significantly increases competitiveness of human umbilical vein endothelial cells (HUVECs) over human aortic smooth muscle cells (HASMCs) both in vitro and in vivo. The strategy proved effective in inducing faster re-endothelialization, inhibiting neointimal formation and restoring vascular homeostasis. The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.
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RSC Advances
·
2024
·Vol. 14
·期 8
·5577-5587
·
IF 3.9
Kai Li,Sinan Tian,Ke Sun,Qingguo Su,Yanhui Mei,Wenjie Niu
Prostate cancer is the most common malignant tumor in the male reproductive system, and its incidence increases with age. Chemotherapy is one of the main strategies for treating prostate cancer, but it often comes with unavoidable side effects. Nanocarriers can improve drug utilization and targeting, and cationic carriers can also carry nucleic acids for gene therapy. In this study, we prepared a cationic micelle constructed from a polyprodrug that can deliver both chemotherapeutic drugs and nucleic acids simultaneously. The typical chemotherapeutic drug hydroxycamptothecin (HCPT) was linked by reactive oxygen species (ROS)-responsive coupling agents and forms amphiphilic block polymers with low molecular weight polyethyleneimine (PEI). The resulting cationic micelles can be triggered by high levels of ROS in tumor cells and collapse to release HCPT and suicide genes to kill tumor cells. At the same time, it reduces the killing of normal cells. In prostate cancer cells, it has been confirmed that the co-delivery carriers combined with chemotherapy and a suicide gene prodrug system have shown an ideal therapeutic effect on prostate cancer.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2024
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IF 8.1
Chengfang Zhang,Zhenyu Song,Chao Li,Qinglong Liu,Jingchun Tang
In the actual polluted environment, the composite pollution system was usually composed of heavy metals and organic pollutants, especially Cr(VI) and chlorophenols often co-existed in industrial wastewater. In this study, a composite material consisting of multilayer graphene carbon shells coated with nZVI (gBC@nZVI) with various excellent properties was applied to deal with the composite system of Cr(VI) and 2,4-dichlorophenol (2,4-DCP) coexisting in the wastewater, and the intrinsic mechanism for the simultaneous removal of heavy metals and organic pollutants was systematically investigated. The results showed that in the composite pollution system (Cr(VI) = 20 mg/L, 2,4-DCP = 15 mg/L), complete removal of Cr(VI) could be achieved in 60 min, while 2,4-DCP achieved 95.2 % removal, with the contribution of oxidative degradation being 76.4 %. It was found that during the efficient adsorption and reduction of Cr(VI) by gBC@nZVI, the generation of the metastable intermediate Cr(V) was verified by probe compounds, electron spin resonance and UV–visible spectroscopy, and further experiments demonstrated that the generation of •OH was closely related to Cr(V) and promoted the oxidative degradation of the coexisting 2,4-DCP. Quenching experiments with the addition of specific scavengers indicated that •OH was the active species directly dominating the oxidative degradation of 2,4-DCP, whereas Cr(V) was indirectly involved in the degradation of 2,4-DCP by promoting the generation of •OH. In addition, the increase of solution pH negatively affected the degradation of 2,4-DCP in the composite polluted system, mainly due to the hindered generation of •OH in the alkaline environment. This work provided theoretical support for the promising application of gBC@nZVI in real environments contaminated with a combination of Cr(VI) and chlorophenols.
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BIOMATERIALS
·
2024
·
IF 12.8
Jiani Huang,Fei Wu,Wenzhao Cao,Yuhan Chen,Qiong Yao,Peili Cen,Jing Wang,Lu Hong,Xiaohui Zhang,Rui Zhou,Chentao Jin,Mei Tian,Hong Zhang,Yan Zhong
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder globally, with no effective treatment available yet. A crucial pathological hallmark of AD is the accumulation of hyperphosphorylated tau protein, which is deteriorated by reactive oxygen species (ROS) and neuroinflammation in AD progression. Thus, alleviation of ROS and inflammation has become a potential therapeutic strategy in many studies. Herein, we reported ultrasmall coordination polymer nanoparticles formed by ferric ions and gallic acid (Fe-GA CPNs), which owned antioxidant and anti-inflammation properties for AD therapeutics. The facilely prepared Fe-GA CPNs exhibited remarkable superoxide dismutase, peroxidase enzyme activity, and ROS eliminating ability with great water solubility, compared with gallic acid. We demonstrated that Fe-GA CPNs effectively relieved oxidative stress, ameliorated inflammation by downregulating TLR4/NF-κB and modulating microglial polarization towards anti-inflammation phenotype, and reduced hyperphosphorylated tau protein levels. Furthermore, Fe-GA CPNs treatment significantly improved cognitive function in tauopathy-induced AD rats, and achieved a neuroprotective effect against AD pathology. This study highlights the potential of coordination polymer nanoparticles as promising therapeutic candidates for AD and other tau-related neurodegenerative diseases.
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ADVANCED MATERIALS
·
2025
·
IF 26.8
Yaqing Kang,Xiaoqing Han,Shijie Zhou,Xingbo Wang,Yanjing Wang,Panpan Song,Xiaochen Su,Mengmeng Qin,Dongyang Qian,Huan Meng,Jiao Yan,Fang Pu,Haiyuan Zhang
Rheumatoid arthritis microenvironment (RAM) contains complex pathogenic mediators that interact dynamically to drive the progression of rheumatoid arthritis (RA). However, most current RA treatments are single-target interventions, exerting limited impact on RAM. Herein, apoptotic extracellular vesicles (ApoEV) are constructed for programmable regulation of the neutrophil-macrophage-ROS pathogenic axis, aiming to reconstruct RAM and improve RA therapy. Mesenchymal stem cells (MSCs) are pretreated with dexamethasone (Dex) and induced apoptosis to produce Dex-loaded and FasL-overexpressing ApoEV (D@ApoEV FasL ), which is further modified with low-molecular-weight heparin (LMWH) through a ROS-responsive cleavage linker to form D@ApoEV FasL ∩L. After intravenous injection into RA mice, D@ApoEV FasL ∩L targeted the inflamed joints based on their MSC-derived feature and blocked neutrophil recruitment through binding to P-selectin on vascular endothelial cells. In response to high ROS, D@ApoEV FasL ∩L shed LMWH and exposed FasL, inducing neutrophil apoptosis through the Fas/FasL signaling pathway. Subsequently, the apoptotic neutrophils triggered macrophage reprogramming from M1 to M2 phenotype, and the released Dex significantly reduced the oxidative damage. Various in vitro and in vivo assessments have confirmed that D@ApoEV FasL ∩L can effectively regulate neutrophils, macrophages, and ROS, trigger an immune cascade, and restore intra-articular immune homeostasis, exhibiting an effective RAM reconstruction ability and a promising therapeutic effect for RA.
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